Page URL:

Study reveals complex interactions between disease genes

12 July 2010
Appeared in BioNews 566

A US study looking at the interaction between genes known to cause a rare genetic disease has shown that common and rare genetic variants interact to make symptoms more or less severe. These results may have major implications for how genetic studies are interpreted, according to the study authors, because it is highly likely that such interactions occur in other genetic conditions.

Professor Nicholas Katsanis and his colleagues at Duke University used zebrafish to study the effect of variations in the 14 genes associated with Bardet-Biedl syndrome (BBS), a rare cellular disorder. BBS can cause symptoms including blindness, heart problems and physical and mental retardation.

The researchers disrupted the fish versions of each of the 14 BBS genes to create mutant phenotypes, and then determined the ability of the 125 known human variants to restore the normal phenotype.

Many of these variants were thought to be benign and able to restore the phenotype, just like a wild type version. But they discovered that - for the majority of these variants - a spectrum of severity was observed, with some partially restoring the phenotype and others showing no improvement at all. Some (28 per cent) of the variants made the phenotype significantly worse.

Genetic studies traditionally focus on the search for rare variants, as the contribution of common variation is generally thought to be minor, but this study showed that common variations can also be detrimental to protein function.

The study is published in PNAS (Proceedings of the National Academy of Sciences).

Functional analyses of variants reveal a significant role for dominant negative and common alleles in oligogenic Bardet Biedl syndrome
PNAS |  8 June 2010
Genetics: Gene plus gene
Nature |  1 July 2010
12 September 2011 - by Mehmet Fidanboylu 
It is hoped that a new method for studying cell development could lead to cures for diseases such as cancer, UK scientists have reported...
6 June 2011 - by Dr Lux Fatimathas 
The link between genetic markers and disease risk is often overstated, say American and Greek researchers. The scientists reviewed the associations identified in highly cited studies, where there was subsequent data available from larger studies...
5 July 2010 - by Dr Marianne Kennedy 
Scientists have discovered a genetic mutation that may make some women less likely to respond to the ovarian stimulating hormones used in fertility treatment. Dr Maria Lalioti and her colleagues from Yale University Medical School, US, reported their findings at the 26th annual meeting of the European Society of Human Reproduction and Embryology in Rome last week...
5 July 2010 - by Victoria Kay 
US scientists have shown for the first time how a virus, a toxin and a genetic mutation interact to cause Crohn's disease. The study, in mice, may help explain why many people with disease risk genes don't develop the condition...
5 July 2010 - by Dr Tamara Hirsch 
Scientists have identified 12 new gene variants associated with type 2 diabetes, according to recent work published in Nature Genetics...
to add a Comment.

By posting a comment you agree to abide by the BioNews terms and conditions

Syndicate this story - click here to enquire about using this story.